Recently, anisometric structures, which are popular in nature but uncommon in artificial materials, have been actively investigated for the development of novel materials designed for sensors, optical systems, scaffolds, etc. In this study we investigated the hypothesis that the symmetry of two-compartment hydrogels influences their temperature responsive behavior and drug diffusivity. Composite hydrogels with isometric and anisometric compartments were prepared using poly(N-isopropylacrylamide), poly(acrylamide), and nanoclay. The anisometric hydrogel showed a markedly smaller volume transition and equilibrium swelling ratio than its isometric counterpart, possibly because of more restriction from the two-compartment structure. Furthermore, water retention and the release of cilostazol were significantly sustained in the case of the anisometric hydrogel. By incorporating Ag nanoparticles into one compartment, an IR responsive transition was achieved, which showed the consistent effect of the anisometric structure. Finite element analysis further confirmed the difference found in the experimental results by presenting a prevailing von Mises stress in the anisometric case. This study provides a novel engineering strategy for hydrogel properties and a fundamental understanding valuable for designing anisometric hydrogel materials.